Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation

NEIMAN, GABRIEL; SCARAFÍA, MARÍA AGUSTINA; LA GRECA, ALEJANDRO; SANTÍN VELAZQUE, NATALIA L.; GARATE, XIMENA; WAISMAN, ARIEL; MÖBBS, ALAN M.; KASAI-BRUNSWICK, TAIS HANAE; MESQUITA, FERNANDA; MARTIRE-GRECO, DAIANA; MORO, LUCÍA N.; LUZZANI, CARLOS; BASTOS CARVALHO, ADRIANA; SEVLEVER, GUSTAVO E.; CAMPOS DE CARVALHO, ANTONIO; GUBERMAN, ALEJANDRA S.; MIRIUKA, SANTIAGO G.

Scientific Reports

Springer Nature

Año: 2019 vol. 9

The stem cell niche has a strong infuence in the diferentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment.However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell diferentiation. To evaluate this, we performed a profle of integrins expression in two stages of cardiac diferentiation: mesodermal progenitors and cardiomyocytes.We found an active regulation of the expression of diferent integrins during cardiac diferentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a signifcant downregulation in cardiomyocytes. To analyze the efect of α5 subunit, we modifed its expression by using a CRISPRi technique. After its downregulation, a signifcant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development wassignifcantly afected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte diferentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.